There are two known strains of HSV: Herpes Simplex Virus Type 1 (HSV-1), which commonly causes herpes labialis (cold sores) and keratitis; and Herpes Simplex Virus Type 2 (HSV-2), which commonly causes genital herpes. The time of initial herpes infection is often obscure and may pass unnoticed. A salient feature of HSV infections is the ability of the virus to remain dormant, most likely within the nervous system ganglia, and then be reactivated. Various factors are thought to trigger these recurrent herpetic episodes, including physical and/or emotional stress, overexposure to sunlight, and certain foods and drugs.
Upon reactivation, the latent HSV begins to replicate and then travels, via the axons, to a peripheral site, where it may shed asymptomatically or cause lesion formation. The differential conditions under which the reactivated virus causes lesions or is shed asymptomatically are not clear. However, asymptomatic shedding is thought to be a factor in the unchecked spread of herpetic diseases, particularly genital herpes.
An estimated 70-80% of the adult population in the United States shows antibodies to HSV-1, indicating past infection with the virus. Geographic location, socioeconomic status, and age, all influence the frequency of HSV. In Brazilian Indians, HSV antibodies are present in 95% of children by age 15. One study at a New Orleans clinic similarly revealed the presence of HSV antibodies in over 90% of children by age 15. Studies in Atlanta and Houston have shown 70-80% seroconversion by early adolescence [Rawls and Campione-Piccardo, Epidemiology of herpes simplex virus type 1 and 2 (1981) in "The Human Herpesvirus: An Interdisciplinary Perspective,"A. Nahmias, W. Dowdle and R. Schenazi, pp. 137-152,Elsevier, North Holland Amsterdam].
Infection with HSV-2 has become increasingly prevalent in the United States. "The estimated number of physician-patient consultations for genital herpes increased fifteen fold between 1966 and 1984, from 29,560 to 450,576. First Office visits--a more likely indicator of newly acquired infection--increased ninefold, from 17,810 in 1966, to 156,720 in 1984." ["Genital Herpes Infections," U.S. 1966-1984, Centers for Disease Control Morbid Mortal Weekly, Vol. 35:402, 1986]. Chronic, ulcerative, genital herpes is often seen in, and may be diagnostic of, individuals with Acquired Immune Deficiency Syndrome (AIDS).
Presently, HSV infections are treated with antiviral agents that interfere with viral replication. Stoxil (5-iodo-2deoxyuridine), Viroptic (trifluorothymidine), and Acyclovir (9-(2-Hydroxyethoxymethyl) guanine), all need to be incorporated into the viral DNA to exert their antiviral activity. [Kaufman H. E. Proc. Soc. Exp. Biol. Med. 109: 251-252 (1962); Elion G. B. et al. Proc. Natl. Acad. Sci. U.S.A. 74: 5716-5720 (1977); Shaeffer H.J. et al. Nature (London) 272: 583-585 (1978); Sugar J. et al. Invest. Ophthal. 12: 532 (1973); Wellings P. C. et al. Amer. J. Ophthal. 73: 932-42 (1972)].
Acyclovir, the current drug of choice for treating HSV, is available in intravenous (IV), topical and oral forms. However, it is most effective in treating primary herpetic infections and is less effective in either preventing or treating recurrent infections [Bryson Y. J. et al. New Engl. J. Med. 308: 916-921 (1983); Mertz G. J. et al. J. Amer. Med. Assoc. 252: 1147-1151 (1984)]. Continuous administration of acyclovir suppresses the number of recurrences, but the frequency of recurrences reverts to its original status when the drug is discontinued [Douglas J. M. et al. New Engl. J. Med. 310: 1551-1556 (1984); Kinghorn G. C. et al. Gentourin. Med. 61: 387-390 (1985); Straus S .E. et al. New Engl. J. Med. 310: 1545-1550 (1984)].
Drugs are also known which suppress viral growth by mechanisms other than those which directly interfere with viral DNA. Smooth muscle relaxing agents, such as Verapamil and Papaverine have been shown to inhibit the replication of cytomegalovirus and influenzae virus
[Albrecht T. et al. Proc. Soc. Exp. Bio. Med. 186: 41-46 (1987); Nugent K. M. et al. Archives of Virology 81: 163-170 (1984)]. Non-steroidal anti-inflammatory drugs are known to inhibit the multiplication of several viruses, including Sindbis, Influenzae A2, HSV, and vaccinia [Inglot A. D. Comparison of the antiviral activity in vitro of some non-steroidal drugs. J. Gen. Virol. 4: 203-214 (1969)]. Lithium, a psychoactive drug, has been found to cause the remission of HSV infections in patients under systemic treatment [Lieb J. New Engl. J. Med. 301: 942 (1979); Trousdale M. D. et al. Antimicrob. Agents Chemother. 25: 522-523 (1984)]. Subsequently, lithium succinate was used as a topical treatment for genital herpes [Skinner G. R. B. The Lancet 2: 288 (1983)]. Most recently, orally administered piracetam was observed to affect beneficially the outcome of myoclonus in an individual with herpes simplex encephalitis. [Karacostas D. et al. Acta Therapeutica 14: 293-299 (1988)].